The invention relates generally to devices and methods for polarizing samples for use in magnetic resonance imaging (MRI).
The present invention relates to nuclear magnetic resonance (NMR) analysis, particularly to nuclear magnetic resonance imaging (MRI) and analytical high-resolution NMR spectroscopy. MRI is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially harmful radiation such as X-rays. Analytical high resolution NMR spectroscopy is routinely used in the determination of molecular structure.
MRI and NMR spectroscopy lack sensitivity due to the normally very low polarization of the nuclear spins of the samples used. A number of techniques exist to improve the polarization of nuclear spins in the solid phase. These techniques are known as hyperpolarization techniques and lead to an increase in sensitivity. In hyperpolarization techniques, a sample of an imaging agent, for example C13 Pyruvate or another similar polarized metabolic imaging agent, is introduced or injected into the subject being imaged. As used herein, the term “polarize” refers to the modification of the physical properties of a solid material for further use in MRI. Further, as used herein, the term “hyperpolarized” refers to polarized to a level over that found at room temperature and 1 T, which is further described in U.S. Pat. No. 6,466,814. However, in order to exploit the NMR signal for in vivo medical imaging the polarized sample must be brought into solution before being introduced into the imaging object. In addition, for in vitro analytical NMR spectroscopy, it can also often be advantageous to bring the polarized solid sample into solution. Techniques are now being developed which involve ex vivo polarization of imaging agents, prior to administration and MR signal measurement. In some instances, the imaging agent undergoes hyperpolarization remote from its end use, at the MRI scanner. A problem exists for ex vivo polarization in that the polarized solid sample has to be brought into solution and transferred into the NMR magnet with a minimal loss of polarization. U.S. Pat. No. 6,466,814 describes an apparatus and method for dissolving solid polarized samples. In this method the polarized sample was manually lifted out of the cryostat and within about 1 second dissolved in deuterium oxide at 40° C., while being subjected to a magnetic field of 0.4 T. This method enhanced the polarization by a factor of up to 21 compared to other methods of producing a solution containing polarized sample.
Further, in current contemplated techniques in order to produce an apparatus that can produce samples with a high polarization, the NMR equipment needs to be provided with a low temperature space that is in a magnetic field. In order to achieve this, any ordinary NMR magnet that has a suitably wide bore size may be equipped with a flow cryostat and instrumentation in order to enable the production of solutions of molecules with enhanced nuclear polarization. A flow cryostat is a vacuum insulated chamber that may be inserted into the bore of a magnet normally may be designed to have a room temperature bore, thereby allowing the temperature of the bore to be lowered by a stream of a cold cryogen. The flow cryostat is usually connected to an external cryogen supply through a transfer line and pumping device, and the flow of cryogen into the flow cryostat cools the bore of the magnet and forms a low temperature space. The flow cryostat may be equipped with means to enable the polarization of solid samples by various polarization techniques and it may be equipped with instrumentation for the detection of nuclear signals in the solid state and in solution. Typically, in dedicated systems for NMR analysis or production of hyperpolarized imaging agents, the low temperature space is preferably integrated into the magnet cryostat. Thus, current hyperpolarization systems and techniques require cooling means in the form of a cold cryogen in addition to the cryogens required for cooling the magnet in the MRI system. There are various practical and environmental challenges associated with cryogen storage and maintenance. Additionally, there are challenges in the clinical setting associated with handling of cryogens. Therefore there is a need to explore opportunities to reduce the cryogen usage in MRI systems and therefore there is a need for a reduced cryogen or cryogen-free hyperpolarization device and methods thereof.